The main aim of this projects is to identify the genetic and/or molecular cause(s) of obesity in humans. We use gene sequencing techniques to identify polymorphisms in obesity target genes. We use a human neurobiology microarray to study the differential gene expression in post-mortem brain samples from obese and lean adult donors. In the past year we have: a) excluded the role of 4 small regions on chromosome 11, 15, 16 and X previoulsy identified by AFLP as potentially harboring polymorphisms linked to obesity; b) studied SNPs in the VNTR region of the insulin gene (INS); c) initiated the identification of SNPs in the fatty acid synthase gene (FAS); d)initiated a collaborative effort with other institutions to create a brain bank specialized in brain samples from obese donors; e) completed gene expression exeriments in the hypothalami of 3 obese and 3 lean donors; f) initiated an exploratory study to use proteomics for the identification of proteins differentially secreted in the CSF of Pimas and Caucasians